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Free access | 10.1172/JCI106725

The inhibition by methylmalonic acid of malate transport by the dicarboxylate carrier in rat liver mitochondria: A possible explanation for hypoglycemia in methylmalonic aciduria

M. L. Halperin, C. M. Schiller, and I. B. Fritz

Department of Medicine, University of Toronto, Toronto 181, Canada

Banting and Best Department of Medical Research, University of Toronto, Toronto 181, Canada

Find articles by Halperin, M. in: PubMed | Google Scholar

Department of Medicine, University of Toronto, Toronto 181, Canada

Banting and Best Department of Medical Research, University of Toronto, Toronto 181, Canada

Find articles by Schiller, C. in: PubMed | Google Scholar

Department of Medicine, University of Toronto, Toronto 181, Canada

Banting and Best Department of Medical Research, University of Toronto, Toronto 181, Canada

Find articles by Fritz, I. in: PubMed | Google Scholar

Published November 1, 1971 - More info

Published in Volume 50, Issue 11 on November 1, 1971
J Clin Invest. 1971;50(11):2276–2282. https://doi.org/10.1172/JCI106725.
© 1971 The American Society for Clinical Investigation
Published November 1, 1971 - Version history
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Abstract

We report the effects of methylmalonic acid (MMA) on the mitochondrial transport systems for malate, α-oxoglutarate, and isocitrate. MMA is shown to be a substrate for all three carrier systems, and an inhibitor of the malate-phosphate exchange carrier. The effects of MMA on the metabolism of malate, oxoglutarate, and isocitrate by rat liver mitochondria are demonstrated to be mediated by the influence of MMA on the transport step. A hypothesis regarding the metabolic impairments responsible for hypoglycemia and ketonemia in methylmalonic aciduria is formulated in relation to these findings.

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